ROLE OF PROTEIN-KINASE-C ISOZYMES IN ACTIVATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN CHRONICALLY INFECTED PROMONOCYTIC CELLS - EVIDENCE AGAINST A ROLE OF PKC-BETA-I

Protein kinase C (PKC) plays an important role in activation of human immunodeficiency. virus type 1 (HIV-1). Because of a molecular and bio chemical heterogeneity of PKC, we have studied the effects of PKC isoz ymes in HIV-1 activation in a latently infected promonocytic cell line , U1, using various PKC isozyme agonists. 12-Deoxyphrbol 13-phenylacet ate (dPP), an agonist of both Ca++-dependent and Ca++-independent isoz ymes, and thymeleatoxin (TI), an agonist of Ca++-dependent PKC isozyme s, induced HIV-1 production at 10 nM with increase in a concentration dependent manner, whereas 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), an PKC beta I isozyme agonist,did not induce viral production at 100 nM. We verified that dPPA induced translocation of PKC beta iso zyme with the isozyme-specific monoclonal antibody usingflow cytometry . This study demonstrates that activation of PKC isozymes leads to an induction of latent HIV-1 in U1 cells whereas PKC beta I isozyme may n ot be important. (C) 1994 Academic Press, Inc.